Immunization of mice with bacterial superantigens (SAg) causes the deletion of SAg-reactive CD4 T cells. The extent of deletion is dose-dependent and single high doses or repeated low doses of the SAg causes deletion of a larger fraction of the reactive CD4 T cells. The remaining SAg-reactive CD4 T cells in the immunized animals are anergic, as they fail to respond to the immunizing SAg both in vivo and in vitro. The anergic CD4 population in SAg-immunized mice has been extensively studied. Again, depending on the immunization protocol, the unresponsiveness of the anergic cells varies and in some instances, the cells even fail to respond to IL-2.
Reports from several laboratories have demonstrated that the anergic CD4 T-cell population induced in mice repeatedly immunized with SAg, in addition to inherently non-responsive T cells, also contains Treg that can suppress an immune response to the antigen both in vivo and in vitro.
Antigen-specific T-cell proliferation was POTENENTLY INHIBITED in the repeatedly immunized mice and cells from such mice were ANERGIC UPON TRANSFER TO NAÏVE RECIPIENTS.
It was shown that repeated antigen stimulation caused potent in vivo T-cell anergy. Thus, CD4 T cells from repeatedly immunized mice proliferated poorly in response to antigen challenge in an adoptive host.
In vivo exposure to bacterial superantigen (SAg) selectively induces the rapid proliferation of T cells carrying SAg-specific TCR Vβ fragments . This is associated with the release of various cytokines such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-γ and tumor necrosis factor (TNF)-α into the circulation. After their initial expansion, T cells undergo activation-induced cell death, or apoptosis, leading to the clonal deletion of SAg-reactive CD4+ and CD8+ T cells from the periphery. SAg-reactive T cells which escape death, however, fail to proliferate and to secrete IL-2 in response to subsequent SAg exposure. This phenomenon, often referred to as anergy, is specific for SAg-reactive T cells, since responsiveness to non-cross-reactive SAg remains normal.
MOLECULAR MIMICRY OF THE SPIKE PROTEIN “TURNS OFF” T-CELLS TO MAINTAIN TOLERANCE
T cell tolerance can be experimentally induced in vivo in a number of different ways. For example, repeated exposures to low doses of protein Ag either by injection or by oral or nasal administration lead to initial activation of responding T cells followed by deletion and anergy in the remaining T cells. Other investigators have used model systems in which TCR-transgenic (TG) T cells are constitutively exposed to their ligands as neo-self-Ags in vivo, which also result in tolerance in the reactive T cells. It has been demonstrated that such in vivo-tolerized CD4+ T cells are not necessarily devoid of effector functions, but rather mediate active suppression of Ag-specific immune responses. Interestingly, T cells anergized in vitro have been found to adopt regulatory T cell functions as well. One common denominator of these different models is that the responding T cells encounter the Ag in the absence of adjuvants activating the APCs. Indeed, several of the in vitro anergy induction protocols made use of agents that interfere with APC functions.
What I believe this leads to, in the case of the Spike Protein, is that since it has such a massive peptide sharing with self-peptides, the IMMUNE SYSTEM PAUSES! It retracts, afraid to take even “baby steps” at attacking ANYTHING for fear it will start destroying self.
The IMMUNE SYSTEM IS PARALYZED DUE TO THE CONSTANT PRESENTATION OF SELF-PEPTIDES TO ANTIGEN PRESENTING CELLS IN THE PRESENCE OF THE SPIKE PROTEIN.
Again, Spike Protein Accelerants cause a massive Ritardando leading to an Immune Morendo.
Chronic exposure to superantigen induces regulatory CD4 T cells with IL-10-mediated suppressive activity